scholarly journals Monogenic diabetes mellitus in Norway

2013 ◽  
Vol 23 (1) ◽  
Author(s):  
Oddmund Søvika ◽  
Henrik Underthun Irgens ◽  
Janne Molnes ◽  
Jørn V. Sagena ◽  
Lise Bjørkhaug ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Testing ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
University Hospital ◽  
Diagnosis And Prognosis ◽  
Hnf1a Gene ◽  
Choice Of Therapy

Here, we review data on monogenic diabetes mellitus in Norway based on the Norwegian MODY Registry at Haukeland University Hospital, Bergen. This registry comprises established or suspected cases of maturity-onset diabetes of the young (MODY) referred to our laboratory for genetic testing. We also present data on neonatal diabetes, another group of monogenic diabetes. To date, we have genetically diagnosed nearly 500 MODY cases in Norway. Mutations in the HNF1A gene (MODY3) were detected in about 50% of families with clinical MODY. GCK-MODY (MODY2) was the second most prevalent type, but may be underreported. We have also found mutations in the monogenic genes ABCC8, CEL, HNF1B, HNF4A, INS, KCNJ11 and NEUROD1. Based on genetic screening in the Norwegian MODY Registry and HUNT2, we estimate the number of MODY cases in Norway to be at least 2500-5000. Founder effects may determine the geographical distribution of MODY mutations in Norway. The molecular genetic testing of MODY and neonatal diabetes is mandatory for correct diagnosis and prognosis as well as choice of therapy

scholarly journals Molecular and clinical characteristics of monogenic diabetes mellitus in southern Chinese children with onset before 3 years of age

2020 ◽  
Vol 8 (1) ◽  
pp. e001345
Author(s):  
Yunting Lin ◽  
Huiying Sheng ◽  
Tzer Hwu Ting ◽  
Aijing Xu ◽  
Xi Yin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Testing ◽  
Age Of Onset ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Chinese Patients ◽  
Combination Strategy ◽  
Southern Chinese ◽  
Whole Exome ◽  
Design And Methods

IntroductionA specific molecular diagnosis of monogenic diabetes mellitus (MDM) will help to predict the clinical course and guide management. This study aims to identify the causative genes implicated in Chinese patients with MDM with onset before 3 years of age.Research design and methods71 children with diabetes mellitus (43 diagnosed before 6 months of age, and 28 diagnosed between 6 months and 3 years of age who were negative for diabetes-associated autoantibodies) underwent genetic testing with a combination strategy of Sanger sequencing, chromosome microarray analysis and whole exome sequencing. They were categorized into four groups according to the age of onset of diabetes (at or less than 6 months, 6 to 12 months, 1 to 2 years, 2 to 3 years) to investigate the correlation between genotype and phenotype.ResultsGenetic abnormalities were identified in 39 of 71 patients (54.93%), namely KCNJ11 (22), ABCC8 (3), GCK (3), INS (3), BSCL2 (1) and chromosome abnormalities (7). The majority (81.40%, 35/43) of neonatal diabetes diagnosed less than 6 months of age and 33.33% (3/9) of infantile cases diagnosed between 6 and 12 months of age had a genetic cause identified. Only 11.11% (1/9) of cases diagnosed between 2 and 3 years of age were found to have a genetic cause, and none of the 10 patients diagnosed between 1 and 2 years had a positive result in the genetic analysis. Vast majority or 90.48% (19/21) of patients with KCNJ11 (19) or ABCC8 (2) variants had successful switch trial from insulin to oral sulfonylurea.ConclusionsThis study suggests that genetic testing should be given priority in diabetes cases diagnosed before 6 months of age, as well as those diagnosed between 6 and 12 months of age who were negative for diabetes-associated autoantibodies. This study also indicates significant impact on therapy with genetic cause confirmation.

Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

2020 ◽  
Vol 16 (8) ◽  
pp. 807-819 ◽  
Author(s):  
Madalena Sousa ◽  
Jácome Bruges-Armas
Keyword(s):  
Diabetes Mellitus ◽  
Complex Disease ◽  
Clinical Manifestations ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Diabetes Genetics ◽  
Individualize Treatment

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene

2020 ◽  
Vol 33 (12) ◽  
pp. 1605-1608
Author(s):  
Xiao Qin ◽  
Jingzi Zhong ◽  
Dan Lan
Keyword(s):  
Diabetes Mellitus ◽  
Novel Mutation ◽  
Male Infant ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Rare Form ◽  
Case Presentation ◽  
Abcc8 Gene

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life.Case presentationWe report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up.ConclusionsThis report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus

1999 ◽  
Vol 134 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Susan L. Christian ◽  
Barry H. Rich ◽  
Charli Loebl ◽  
Jeannette Israel ◽  
Rohitkumar Vasa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Testing ◽  
Uniparental Disomy ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Chromosome 6 ◽  
Paternal Uniparental Disomy

Neonatal Diabetes – From Gene Discovery yo Clinical Practice Changes

2013 ◽  
Vol 20 (3) ◽  
pp. 343-352
Author(s):  
Cristian Guja ◽  
Loreta Guja ◽  
Constantin Ionescu-Tîrgovişte
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Single Gene ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Special Focus ◽  
Sulphonylurea Treatment ◽  
The Common

Abstract Diabetes mellitus is one of the most common chronic diseases but also one of the most heterogeneous. Apart the common phenotypes of type 1 and type 2 diabetes, around 1-2% of all cases arise from a single gene mutation and are known as monogenic diabetes. Diabetes diagnosed within the first 6 months of life is known as neonatal diabetes and has been extensively studied during the last two decades. Unraveling the genetic cause and molecular mechanism of this rare diabetes phenotype led to a dramatic change in the treatment of these children who often can be switched from insulin to sulphonylurea treatment. The aim of this paper is to review the known genetic causes of neonatal diabetes and to highlight the most recent aspects of the disease caused by mutations in the KATP and insulin genes, with a special focus on the individualized treatment of these cases

scholarly journals Multimorbidity in Pediatric Dermatology: Clinical Case

2020 ◽  
Vol 19 (6) ◽  
pp. 483-489
Author(s):  
Nikolay N. Murashkin ◽  
Alexander I. Materikin ◽  
Eduard T. Ambarchian ◽  
Roman V. Epishev ◽  
Leonid A. Opryatin ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Autosomal Recessive ◽  
Clinical Case ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Final Diagnosis ◽  
Molecular Genetic Testing ◽  
Pediatric Dermatology ◽  
Dominant Type ◽  
Recessive Type

Background. Nowadays, dermatoses with mixed clinical picture and resistant to classical management become more common. The presence of various genetic disorders typical for most chronic dermatoses may indicate possible combination of several nosologies.Clinical Case Description. The article presents the clinical case of multimorbid condition in 10 years old patient who has nucleotide variants in CARD14 and EXPH5 genes. Mutations in CARD14 gene are typical for patients with type 2 psoriasis and pityriasis rubra pilaris (autosomal dominant type), while mutations in EXPH5 gene are typical for patients with non-specific epidermolysis bullosa (autosomal recessive type). Mutation in the TGM1 gene that is described in patients with congenital ichthyosis (autosomal recessive type), pathogenic mutations in KRT74 gene typical for ectodermal dysplasia, hypotrichosis and uncombable hair syndrome, and mutations in the KRT86 gene typical for monilethrix were also revealed. Medical history taking and histological examination as well as clinical data evaluating are crucial for correct diagnosis. They allow to understand the absence of the such manifestations in relatives and reveal various pathological processes in the epidermis. Molecular genetic testing with new generation sequencing (NGS) helps to finally establish the diagnosis and determine the further tactics for patient management.Conclusion. Multidisciplinary approach and use of high-technology methods of examination and treatment (such as molecular genetic testing and biological therapy) are required for final diagnosis in severe forms of chronic dermatosis resistant to treatment and for decision on correct tactics for the further management of such patients.

Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing

2005 ◽  
Vol 152 (6) ◽  
pp. 1353-1356 ◽  
Author(s):  
M. Akiyama ◽  
Y. Tsuji-Abe ◽  
M. Yanagihara ◽  
K. Nakajima ◽  
H. Kodama ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Molecular Genetic Testing

scholarly journals A case with relapsed transient neonatal diabetes mellitus treated with sulfonylurea, ending chronic insulin requirement

2018 ◽  
Vol 2018 ◽  
Author(s):  
Akihiko Ando ◽  
Shoichiro Nagasaka ◽  
Shun Ishibashi
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Testing ◽  
Glycaemic Control ◽  
Genetic Defect ◽  
Neonatal Diabetes ◽  
Insulin Requirement ◽  
Neonatal Diabetes Mellitus ◽  
List Type ◽  
Sulfonylurea Receptor ◽  
Early Screening

Summary We report a case of a woman with diabetes mellitus caused by a genetic defect in ABCC8-coding sulfonylurea receptor 1 (SUR1), a subunit of the ATP-sensitive potassium (KATP) channel protein. She was diagnosed with diabetes at 7 days after birth. After intravenous insulin drip for 1 month, her hyperglycaemia remitted. At the age of 13 years, her diabetes relapsed, and after that she had been treated by intensive insulin therapy for 25 years with relatively poor glycaemic control. She was switched to oral sulfonylurea therapy and attained euglycaemia. In addition, her insulin secretory capacity was ameliorated gradually. Learning points: Genetic testing should be considered in any individuals or family with diabetes that occurred within the first year or so of life. Sulfonylurea can achieve good glycaemic control in patients with KATP channel mutations by restoring endogenous insulin secretion, even if they were treated with insulin for decades. Early screening and genetic testing are important to improve the prognosis of patients with neonatal diabetes mellitus arising from ABCC8 or KCNJ11 mutation.

scholarly journals Clinical Utility of the Addition of Molecular Genetic Testing to Newborn Screening for Sickle Cell Anemia

2021 ◽  
Vol 8 ◽  
Author(s):  
Lisa M. Shook ◽  
Deidra Haygood ◽  
Charles T. Quinn
Keyword(s):  
Genetic Testing ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Final Diagnosis ◽  
The United States ◽  
Molecular Genetic Testing ◽  
Benign Condition

Sickle cell disease (SCD) is a group of related yet genetically complex hemoglobinopathies. Universal newborn screening (NBS) for SCD is performed in the United States and many other nations. Classical, protein-based laboratory methods are often adequate for the diagnosis of SCD but have specific limitations in the context of NBS. A particular challenge is the differentiation of sickle cell anemia (SCA) from the benign condition, compound heterozygosity for HbS and gene-deletion hereditary persistence of fetal hemoglobin (HbS/HPFH). We describe a sequential cohort of 44 newborns identified over 4.5 years who had molecular genetic testing incorporated into NBS for presumed SCA (an “FS” pattern). The final diagnosis was something other than SCA in six newborns (12%). Three (7%) had HbS/HPFH. All had a final, correct diagnosis at the time of their first scheduled clinic visit in our center (median 8 weeks of age). None received initial counseling for an incorrect diagnosis. In summary, genetic testing as a component of NBS for SCD is necessary to provide correct genetic counseling and education for all newborns' families at their first visit to a sickle cell center. Genetic testing also permits the use of early, pre-symptomatic hydroxyurea therapy by preventing infants with HbS/HPFH from receiving unnecessary therapy. We argue that genetic testing should be incorporated into contemporary NBS for SCD.

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